ANTIAPOPTOTIC MECHANISM FOR THE IMPLEMENTATION OF THE HEPATOPROTECTIVE EFFECT OF PYRIMIDINE DERIVATIVESAbstract
The present study aimed to study the effect of the drug Xymedon and its conjugate with L-ascorbic acid exhibiting hepatoprotective activity on the apoptosis of rat liver cells against the background of the influence of hepatotoxic agent tetrachloromethane. Though the general effects of Xymedon and its conjugates with various biogenic acids have been studied, the molecular markers affected by the compounds have not yet been established. Experimental methods of investigation included modeling of toxic liver damage by oral administration of carbon tetrachloride to laboratory Wistar rats. To establish the molecular mechanisms of the antiapoptotic effect involved in the hepatoprotective activity of Xymedon and its conjugate with L-ascorbic acid, the level of early apoptosis markers Akt, BAD, BCL-2, p53, Active Caspase-8 Active Caspase-9 in rat liver homogenates was determined by multiplex analysis method using the MagPix system («MerkMillipore», USA). The study showed that Xymedon and its derivative with L-ascorbic acid exhibited an antiapoptotic effect, significantly reducing the number of early apoptosis markers BAD, Active Caspase-9. Also, the derivative with L-ascorbic acid reduces the expression of p53. Moreover, it was shown that some biochemical markers are normalized under the influence of the studied compounds. The results obtained have both scientific value, bringing us closer to the true mechanism of action of pyrimidine derivatives, and practical value – the possibility to create an effective hepatoprotective drug with a strong evidence base and degree of study.
A. A. Parfenov , A. B. Vyshtakalyuk *, I. V. Galyametdinova, V. E. Semenov and V. V. Zobov
Institute of Fundamental Medicine and Biology of Kazan Federal University, 5 Tovarisheskaya Str., Kazan, Russia.
01 March 2022
18 April 2022
25 April 2022
01 October 2022